Real-World Study Reveals Shifting Treatment Patterns and Persistent Unmet Needs in DLBCL

Key Clinical Summary

• A US real-world study of 9875 patients with diffuse large B-cell lymphoma (DLBCL) found that conventional chemoimmunotherapy use declined substantially in second- and third-line treatment between 2016 and 2024, while adoption of novel therapies increased.
• Median overall survival decreased with successive lines of therapy, from 58.1 months in the first-line setting to 30.0 months in the second-line setting and 18.2 months in the third-line setting.
• Among patients receiving chimeric antigen receptor (CAR) T-cell therapy, 93 subsequently received 36 distinct treatment regimens, highlighting the lack of an established treatment approach following CAR T-cell therapy failure.

Treatment patterns for DLBCL have shifted substantially toward novel therapies, including CAR T-cell therapies, antibody-drug conjugates, and bispecific antibodies, according to a large US real-world study. However, survival outcomes continue to decline among patients requiring additional lines of therapy, highlighting persistent unmet needs despite an expanding treatment landscape.

The study, published in Blood Cancer Journal, evaluated treatment patterns and clinical outcomes among commercially insured and Medicare Advantage patients with DLBCL between October 2015 and June 2024. The findings provide insight into how newer treatment options are being incorporated into clinical practice and the challenges associated with managing relapsed or refractory disease.

Real-World Analysis Examines Treatment Patterns Across Lines of Therapy

Researchers conducted a retrospective observational study using Optum's deidentified Clinformatics Data Mart database, which includes medical and pharmacy claims from commercially insured and Medicare Advantage populations across the United States.

The analysis included 9875 patients with DLBCL who received at least 1 line of therapy during the study period.

Patients were evaluated according to treatment line and specific therapies, including first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); second-line stem cell transplantation; and CAR T-cell therapy administered in any treatment line.

Among patients receiving first-line treatment, the mean age was 71.6 years, 53.8% were male, and 78.8% were enrolled in Medicare Advantage.

Investigators assessed overall survival, time to next treatment or death, and treatment failure rates using Kaplan-Meier analyses.

Novel Therapies Gain Ground in Later Treatment Lines

R-CHOP remained the most frequently used first-line regimen throughout the study period, accounting for approximately 62% to 67% of first-line treatments between 2016 and 2023.

However, its use declined to 49.4% during the first half of 2024 as newer treatment options, including polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, and prednisone, became more widely adopted.

Changes were more pronounced in later treatment lines.

In the second-line setting, conventional chemoimmunotherapy and chemotherapy use decreased from 81.6% in 2016 to 41.9% in 2024. During the same period, stem cell transplantation use declined from 11.4% to 4.3%.

By the first half of 2024, 43.0% of patients receiving second-line treatment were treated with novel therapies, including CAR T-cell therapy, polatuzumab vedotin-based regimens, tafasitamab-based regimens, and other immunotherapies.

A similar shift occurred in third-line treatment. Conventional chemoimmunotherapy and chemotherapy use decreased from 47.6% in 2016 to 22.1% in 2024, while novel therapies accounted for 55.9% of third-line regimens.

These findings demonstrate the increasing integration of newer treatment modalities into routine DLBCL management.

Survival Outcomes Decline With Successive Treatment Lines

Despite expanded treatment options, clinical outcomes worsened among patients requiring additional lines of therapy.

Median overall survival declined from 58.1 months (95% CI, 54.2-60.9) in the first-line setting to 30.0 months (95% CI, 27.0-33.0) in the second-line setting and 18.2 months (95% CI, 15.2-20.9) in the third-line setting.

Median time to next treatment or death followed a similar pattern, decreasing from 36.1 months in the first-line setting to 10.6 months in the second-line setting and 7.8 months in the third-line setting.

Treatment failure, defined as initiation of another treatment line or death, remained common.

At 12 months, treatment failure rates were 36.0% following first-line therapy and 51.8% following second-line therapy.

Among patients receiving CAR T-cell therapy, the 12-month treatment failure rate was 42.2%.

These findings underscore the continued challenges of achieving durable disease control, particularly among patients with relapsed or refractory DLBCL.

CAR T-Cell Therapy Outcomes Highlight Treatment Sequencing Challenges

A total of 420 patients received CAR T-cell therapy during the study period.

Among these patients, 35.9% received axicabtagene ciloleucel, 24.5% received lisocabtagene maraleucel, and 6.4% received tisagenlecleucel. The remaining 33.3% had CAR T-cell therapy recorded without a specific product identified.

Among 238 patients with an apheresis claim, the median time between apheresis and CAR T-cell infusion was 33 days. Bridging therapy was documented in 66.0% of these patients.

Median overall survival following CAR T-cell therapy was 26.4 months (95% CI, 22.6-31.9), while median time to next treatment or death was 18.3 months.

Among patients who received additional therapy following CAR T-cell treatment, median overall survival from the start of the subsequent treatment line was 23.3 months, and median time to next treatment or death was 4.8 months.

Notably, 93 patients received 36 distinct treatment regimens after CAR T-cell therapy, indicating substantial variation in treatment selection.

The most frequently used subsequent therapies included loncastuximab tesirine (12.0%), epcoritamab (12.0%), rituximab monotherapy (8.7%), and polatuzumab vedotin plus bendamustine and rituximab (7.6%).

The diversity of post-CAR T-cell regimens highlights the absence of a single established treatment approach for patients requiring additional therapy.

Implications for Managed Care

The findings have important implications for managed care organizations as the DLBCL treatment landscape continues to evolve.

The increasing use of CAR T-cell therapies, antibody-drug conjugates, and bispecific antibodies introduces new considerations for treatment sequencing, formulary management, and specialty care coordination.

Although these therapies have expanded treatment options, the continued decline in survival and time to next treatment across successive lines suggests that significant unmet needs remain.

The findings also highlight the complexity of managing patients following CAR T-cell therapy. The use of 36 different subsequent regimens among 93 patients suggests substantial variability in clinical practice, which may complicate treatment pathway development and resource planning.

For payers and health systems, additional real-world evidence comparing clinical effectiveness, treatment-related resource utilization, and costs may help inform coverage policies and evidence-based treatment pathways.

However, the study did not directly evaluate treatment costs or compare the effectiveness of individual regimens. Its retrospective claims-based design also introduces potential limitations related to treatment classification, incomplete clinical information, and differences in patient characteristics across treatment groups.

Additionally, the predominance of Medicare Advantage beneficiaries may limit the generalizability of findings to younger commercially insured populations or patients covered by other insurance programs.

Conclusion

This real-world US analysis demonstrates a substantial shift toward novel therapies in second- and third-line DLBCL treatment between 2016 and 2024.

Despite these advances, survival outcomes continued to decline with successive treatment lines, and treatment patterns following CAR T-cell therapy remained highly variable.

The findings underscore the need for additional research evaluating treatment sequencing, comparative effectiveness, and long-term outcomes to support evidence-based clinical and managed care decision-making in DLBCL.

Reference 

Shadman M, Harper JS, Bokun A, et al. Real-world treatment patterns and clinical outcomes among patients with diffuse large B-cell lymphoma in a US healthcare claims database. Blood Cancer J. 2026;16(14). doi:10.1038/s41408-025-01412-8